The failure of biophysics to model bioelectricity

[Gregorio Kelly]

I've seen elsewhere on this forum the standard accounts of bioelectricity and the nature of the nerve impulse. I ask you then to consider a different account, one that is concordant with physics, and which debunks the standard account. In doing so it hints at the tremendous potential of the use of electrochemistry to advance longevity and treat debilitation from traumatic nervous injury.

 

The idea prevails that physics is inadequate at describing the complexity of life emergent from chemistry, and that it must be supplemented by biophysics. Even physicist Erwin Schrodinger, in his 1947 What is Life?, hypothesized there may yet be undiscovered laws of physics to explain how life could have arisen and developed given that unlikelihood because of the second law of thermodynamics. This idea is no more evident than in the field of energy and electricity, where the deviation of the life sciences from physics, still impedes the progress of the former. The 1902 hypothesis of Julius Bernstein, to the effect that a voltage would someday be measured across a neuron membrane, and that the voltage would be due to an ion concentration gradient, was an attempt to explain the electricity of the nervous system. Bernstein used the Nernst Equation to justify this hypothesis. The Nernst Equation, according to its author, Walther Nernst, was not about electrical pressure. It was a thermodynamic equation in which the term volt expressed entropic pressure calculated to cause two different solutions to mix when the barrier between them was removed.

 

Bernstein's hypothesis was considered proven when, in the early 1940s, a voltage was measured across the cell membrane. The detection of the voltage did not prove it was due to an ion concentration gradient. This was assumed, however, and in subsequent years the hypothesis was expanded and became known as the ionic channel model of nerve impulse propagation, chemiosmosis, and the proton motive force.

 

In fact the nature of electricity was not understood in its electrical and chemical bonding role, and its place in the periodic table of the elements, for twenty years after Bernstein's hypothesis. Chemical energy was expressed in coulombs whose rate of flow was measured in amperes, a term universally accepted by physicists in 1906. This form of energy was quantized, that is, it occurred in discrete packets known as electrons, whose place in the atom and molecular bonding (ionic and covalent bonds), was still being refined and understood till at least the late 1940s.

 

The ionic channel model of nerve impulse propagation (from Bernstein's unproven hypothesis founded on the arrogation of the subject matter of the Nernst equation for something it was not intended to model) was an attempt to account for the electricity of the nervous system without resort to electrons. It was subsumed under the field of bioenergetics, and regarded as a necessary supplement to prosaic redox coupling. Redox coupling, the movement of electrons from one chemical reaction to another that their arrival caused, was seen as basic electrochemistry, too simple to account for the complexity thought to characterize life. The biological mishandling of electricity became institutionalized. Bertil Hille [Ionic Channels of Excitable Membrane, 1991] writes: "In this heroic time of what can be called classical biophysics (1935-1952) the membrane ionic theory of excitation was transformed from untested hypothesis to established fact...The story illustrates the tremendous power of purely electrical measurements in testing Bernstein's membrane hypothesis."

 

The problem was that biological, theoretical understanding of electricity was so insular and nineteenth century that there was no way that any conclusions drawn from the electrical measurements could be taken as valid. For example, Hille writes: "One can draw an analogy between Ohm's law for electrical flow and the rule for flow of liquids in narrow tubes." This is the pre-twentieth century view of electricity as a fluid, a view that was completely expunged from the physical sciences prior to what Hille calls the heroic time of classical biophysics. In 1980, in a Scientific American article, Pierre Morell and William T. Norton report in their essay "Myelin," in all seriousness that "...the mechanism by which Myelin facilitates conduction has no exact analogy in electrical circuitry," where this mechanism involved fluid electricity that did not rely upon electrons. Without an exact analogy to electrical circuitry, this model, Hille avers, was based upon 'purely electrical measurements.' In the 1991 Principles of Neural Science (3rd edition, Koester, "Cell Membrane Voltages", ed. Kandel, Jessel and Schwartz, and all subsequent editions) can be found 'membrane equivalent circuits' that have no analogy in electrical circuitry, but that use the equations and devices of electrical circuitry (capacitors and resistors) to prove the model.

 

In his 1976 The Understanding of the Brain, John Eccles, who, with Alan Hodgkin and Andrew Huxley, received a Nobel in 1963 for the ionic model, described a key experiment thought to corroborate the model. The presumptuousness of the researchers is truly breathtaking. Eccles writes: "The content of the axon has the consistency of jelly, and for most purposes you can substitute an appropriate salt solution without deteriorating impulse conduction by the fiber. For example Baker and Shaw were able to squeeze out the contents of the giant squid axon with an open end by a kind of microroller, leaving a collapsed, flattened axon that appeared destroyed. Yet when they reinflated it by an appropriate salt solution, a potassium salt, the fiber was restored and conducted well for hours." Here Eccles is claiming that the nerve's electrical functioning is independent of the contents of the axon, and is entirely dependent upon the nature of its surrounding fiber because it is the fiber that permits the flow of electrical fluid made up of ions.

 

The ionic model was embellished upon by Peter Mitchell, who received a Nobel in 1978 for chemiosmosis and what he termed proticity. Mitchell equated ∆pH with electrical voltage, where a ∆pH of 3.5 was equated roughly with 210 mV, on the basis of Nernst calculations, not measurements, of voltage. Proof of the conflation of the two theoretical schemes was alleged to be found in the generation of heat when the ∆pH included the number 7, that is, when acid/base reactions were involved. In such reactions the chemical energy liberated by the formation of ionic bonds was taken as evidence for the validity of Nernst's application to [heat] energy, even though a ∆pH that did not include the number 7 did not result in the liberation of any energy. Ionic bonds gave off energy, unlike the covalent bonds of organic chemistry, that require energy. The model of bioelectricity favored by Mitchell and the bioenergeticists, and propagated by Koester (Principles of Neural Science, 1991), consequently alluded to electrical energy as being dependent upon the separation of charge through the breaking of ionic bonds, as if this were one way to store electrical energy. This method for storing electrical energy is found nowhere in physics, and is used by no one to power anything. For the biophysicist this became a selling point, for it underlined the specialness of life.

 

Furthermore ion currents (as they became known) did not manifest any sort of induced magnetic field when they were said to be in effect, something never tested for by Bernstein or any life scientist that followed, despite that Helmholtz, in the early 1880s, used this affect (the Oersted Affect) to detect the nerve impulse in vivo, and get a solid estimate for the speed of the nerve impulse. This, if nothing else, is a clear indication that electromagnetism and ion currents driven by fluid dynamics, were entirely incommensurable, and that the nerve impulse was electrochemical.

 

Mitchell and the bioenergeticists confused the quantization of chemical energy with the second law of thermodynamics. The idea persists today that the movement of protons and cations in an electrolytic solution is a special form of energy transmission that is characteristically biological and not involving electrons. This is called biophysics. In physics the movement of the same cations and protons in an electrolytic fluid is R in V=IR, and I is expressed in amperes. Yet for the biophysicist the slight attraction of anions to the cathode, and cations to the anode, when a battery providing a voltage discharges into an electrolytic fluid, is an electrical-energy storage device able to be tapped when the battery is turned off. The slight concentrations of ions around the electrodes triggered by battery discharge, dissipate into the bulk solution from thermodynamic forces, not electrical ones, and give off no usable electrical charge by doing so. Yet, for the biophysicist, there is stored, biologically-usablel energy from charge separation triggered by the battery's discharge, and this supplements the redox activity in the battery rather than merely making possible its transmission. So R becomes I, and membrane permeability and capacitance becomes R. This rules out electrochemistry and redox functioning of cellular batteries, since that implies the movement of coulombs, not ions.

 

Life is generally conceived of as the emergence of complexity from chemistry. Emergence is seen as the appearance of organic systems of increasing complexity whose wide variety of mechanisms is combined in such a way as to presumably render the physical sciences irrelevant given reductionist methodology. Reductionism emphasizes analysis of the parts, and is given to deduction; unification or summation of the parts, on the other hand, is often an inductive exercise that precedes reductionist, deductive analysis. The whole is greater than the sum of the parts, the saying goes, manifesting a protean notion of life whose exact origins remain obscure, a subject of disputation, yet a notion that something novel is involved, not given to deductive, theoretical understanding in terms of reductionist physics. One is regaled with the example of a clock where the clock tells time, something none of the parts are capable of without proper assembly and windup.

 

One must not overlook that the clock's time-telling is something dependent upon an observer's reading, and that the regular movement of the assembly is otherwise entirely within the bounds of Newtonian mechanics. Despite the alleged complexity of life, whatever it might be, there is no point at which it transcends the laws of physics. But observers still disagree as to where life begins, and how it is different from clocks. Life, like dualism, is essentially an epiphenomenon, an artifact of conversational categorizations and taxonomies for the ensembles of microscopic chemical occurrences that comprise the biomass. To understand life deductively one must reduce it to its essentials. In the case of life those essentials are two: organic chemistry, and the chemical energy capture necessary for the covalent bonds of organic chemistry. Knowing the nature of the substance of our biological clock, and knowing how it is wound-up and transmits power to the parts of its substance, we can deduce what it will take to slow that wind-down and maintain those parts.

 

Every chemical reaction either takes energy or gives off energy. The generation of the covalent bonds of organic chemistry takes energy. This energy is captured in redox coupling, the efficiency of which is expressed as a ratio of amperes captured to amperes available for capture. The recharge rate of an organic biomass is determined by its size (in grams), the energy available, and the ability of the structure of the mass to capture (absorb and expend) energy from what is available. The duration of the structure, its size (increase, and decrease), its development, and the equilibration of energy through it that appears as motor activity, is directly related to the recharge rates of the structure and its parts. This is expressed in the version of Kleiber's Law containing, in the exponent for biomass, the term metabolic efficiency, where that is the redox ratio of amperes spoken of in the first part of this paragraph.

 

Kleiber's Law is an equation that relates the recharge rate of the covalent bonds of organic biomass, to the size of the biomass. Originally limited to the study of biological energy in terms of heat, the exponent of biomass was argued to be 2/3 since this modeled the rate of heat loss of the biomass to unit of surface area in a circular or slightly ovoid shape. Things became more voluminous (radius to the third power) faster than their surface area (radius to the second power) increased. More massive things lost less heat per unit surface area than smaller things, and were taken to be more efficient at energy retention as a result. But Kleiber declared that the exponent was more likely 3/4 than 2/3, from his studies of the energetics of heat loss in mammals.

 

In 1997 Geoffrey West et al. [Science] argued that the number 3/4 resulted from the increased ability of larger organisms, with hearts, to deliver nutrients to the cells. Vascular branching, the argument went, was fractal-like in nature, and this resulted in an extra Euclidean dimension, in effect. In this model the battery-like nature of the cell was taken to be that of a primary cell, where the energy needs of the cell were the result of the combustion/oxidation of nutrients within the cell, nutrients re-supplied by vascular flow, and whose catabolic/oxidative breakdown was the denominator of the redox-coupling, metabolic efficiency (ME) ratio, with the generation of ATP in the numerator.

 

The analogy of the cell as a primary battery contrasts with the view of it as a secondary cell, a rechargeable battery whose primary characteristics might be supplemented by neuronal discharge to the cells of somatic structures, apart from the arrival of new nutrients delivered by vascular flow. Some chemical reactions within the cell, particularly those dealing with the generation and capture as ATP of energy in the mitochondrion (e.g., the hydrolysis and generation of NADH), are reversible without supplemental intra-cellular oxidation from delivered nutrients. The re-synthesis of NADH from NAD and H+ within the mitochondrion's inner membrane, can be affected by the delivery of chemical energy from neuronal discharge to the somatic structure, where it is conducted to the individual cells' gap junctions. In this sense the cells of the organism are secondary cells. This involves a further increase in metabolic efficiency for the cell, with the numerator increasing while the denominator remains constant. In the sense that this energy arises from the digestive-breakdown of organic molecules in the stomach of the organism in neuro-gastric coupling, the organism is a primary battery, while its cells are secondary batteries. Increased encephalization of organisms then marks their increase in average ME.

 

Since efficiency is measured against loss to heat, the exponent becomes then either (3ME-1)/3ME, or (4ME-1)/4ME, where ME is metabolic efficiency. In either case a graph of the equation using either exponent will resemble the other. For purposes of clarification, 3/4 will be taken to occur at 100% ME, and 2/3 at 89% ME. These values for ME are very unlikely, and not even characteristic of mechanical systems as in clocks, let alone chemical ones.

 

When a graph is made of the equation MR (metabolic recharge rate of covalent bonds) = W (biomass in grams) raised to the power (4ME-1)/4ME, with a different curve for each W, quite a different picture emerges than for the same equation using either 2/3 or 3/4 as the exponent. There seems to be a set of attractors causing all curves to merge at 25% ME and one gram, at which point fluctuations in MR are less drastic given slight changes in ME. What this announces is that thermodynamic tendencies for changes in biomass to temper swings in MR given changes in ME, that is, tendencies for MR equilibrium, pressure for biomass to approach one gram in size, and 25% efficiency. The energetics of organic biomass organization, for all biomass, are the determinant factors behind all aspects of biomass and its behavior, from replication to activity. The numbers reveal then that evolution and origins of life are primarily about metabolism and only secondarily about genetics, and that metabolism includes replication where the latter is change in value for W.

 

None of these things are understandable using biophysics, where redox coupling is considered a small part of life in which genetics rules, where metabolism includes heat generation, and where chemical energy is thought to include ion currents and chemiosmosis.